Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Monoclonal antibody or fragment thereof
Reexamination Certificate
1999-08-05
2001-11-27
Huff, Sheela (Department: 1642)
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
Monoclonal antibody or fragment thereof
C424S130100, C424S133100, C424S134100, C424S152100, C424S153100, C424S155100, C435S326000, C435S328000, C435S330000, C435S332000, C435S344000, C435S346000, C435S354000, C435S440000, C435S449000, C435S451000, C435S452000
Reexamination Certificate
active
06322787
ABSTRACT:
Despite the progress in chemotherapy and radiotherapy in recent years, many malignant diseases in man still have an extraordinarily unfavourable prognosis. Frequently, these diseases can not be definitely cured because following a conventional therapy often residual malignant cells remain in the patient which later result in tumor recidivation. In this respect, great hopes have been placed on immunotherapeutical approaches by which the patient's immune system is induced to reject the tumor. It has been known that tumor-associated antigens exist on tumor cells and that in principle the immune system is capable of recognizing them and of attacking the malignant cells. However, tumors have developed several strategies which enable them to escape the immune response. This is possible by e.g. an insufficient presentation of tumor-associated antigens and/or insufficient activation of the tumor-specific T cells which generally exist. Enhancing antigen presentation is therefore a desirable object to achieve by an immunotherapeutical intervention.
DE 196 34 159.0 describes a method by which the B cell lymphoma immunoglobulin idiotype, i.e. an antigen which is absolutely tumor-specific in this disease, is directed against professional antigen-presenting cells (APCs). For this purpose, a so-called trioma is generated by fusing the lymphoma cells with a hybridoma expressing a specificity against APC surface molecules. This trioma secretes the tumor idiotype in the form of a bispecific immunoglobulin binding to APCs. Following internalization and processing of the idiotype, idiotype-derived peptides are presented on the APCs to the immune system. This results in a more efficient activation of T cells. Tumor-specific T cells may be generated by “professional” presentation of the tumor antigen on the APC in contrast to an incomplete presentation on the tumor cell. We have shown that for induction of a more efficient anti-tumor protection an injection of the modified cells is absolutely required. Treatment with the purified bispecific immunoglobulin failed to achieve an efficient anti-tumor immunity. We suggest that this may be due to an additional immunization against other tumor-associated antigens occuring after lysis of the trioma cells in the animal (or patient) treated. However, this method suffers from the disadvantage that it is applicable only to malignant diseases of B cells.
It is an object of the present invention to provide a novel means of inducing an anti-tumor immunity in a patient wherein said means shall be applicable not only to B cell tumors.
According to the invention said object has been solved by creating a tumor cell of human or animal origin expressing an antibody directed against a surface antigen on an antigen-expressing cell (APC) wherein the tumor cell lacks immunoglobulin derived from the parental tumor, i.e. the tumor cell itself originally did not contain any immunoglobulin. It is only by introduction of immunoglobulin-expressing genes encoding an antibody directed against a surface antigen on an antigen-expressing cell that the tumor cells are equipped with specific immunoglobulin.
REFERENCES:
Kearney, et al. A new mouse myeloma cell line that has lost immunglobulin expression but permits the construction of antibody-secreting hybrid cell lines. The Journal of Immunology 123(4):1548-1550, Oct. 1979.*
Shulman et al. A better cell line for making hybridomas secreting specific antibodies. Nature 276:269-270, 1978.*
Harlow and Lane. Antibodies, A laboratory manual, pp.96-99, 1988.*
ATCC Cell Lines and Hybridomas Catalog, 8th edition, pp. 413 and 419, 1994.*
Kearney, et al. A new mouse myeloma cell line that has lost immunglobulin expression but permits the construction of antibody-secreting hybrid cell lines. The Journal of Immunology 123(4):1548-1550, Oct. 1979.*
ATCC catalog. 8th edition, 1994.*
Harlow and Lane. Antibodies, A laboratory manual, pp.96-99, 1988.
Lindhofer Horst
Mocikat Ralph
GSF Forschungszentrum fur Umwelt und Gesundheit GmbH
Harris Alana M.
Huff Sheela
Townsend and Townsend / and Crew LLP
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